Cytotoxic Effect of a Novel Synthesized Carbazole Compound on A549 Lung Cancer Cell Line.
Increased death rates due to lung cancer have necessitated the search for potential novel anticancer compounds such as carbazole derivatives. Carbazoles are aromatic heterocyclic compounds with anticancer, antibacterial and anti-inflammatory activity. The study investigated the ability of the novel...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4489925?pdf=render |
| _version_ | 1818202585316720640 |
|---|---|
| author | Refilwe P Molatlhegi Alisa Phulukdaree Krishnan Anand Robert M Gengan Charlette Tiloke Anil A Chuturgoon |
| author_facet | Refilwe P Molatlhegi Alisa Phulukdaree Krishnan Anand Robert M Gengan Charlette Tiloke Anil A Chuturgoon |
| author_sort | Refilwe P Molatlhegi |
| collection | DOAJ |
| description | Increased death rates due to lung cancer have necessitated the search for potential novel anticancer compounds such as carbazole derivatives. Carbazoles are aromatic heterocyclic compounds with anticancer, antibacterial and anti-inflammatory activity. The study investigated the ability of the novel carbazole compound (Z)-4-[9-ethyl-9aH-carbazol-3-yl) amino] pent-3-en-2-one (ECAP) to induce cytotoxicity of lung cancer cells and its mechanism of action. ECAP was synthesized as a yellow powder with melting point of 240-247 °C. The 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), lipid peroxidation and comet assays were used to assess the cytotoxic effect of the compound on A549 lung cancer cells. Protein expression was determined using western blots, apoptosis was measured by luminometry (caspase-3/7, -8 and -9) assay and flow cytometry was used to measure phosphatidylserine (PS) externalisation. ECAP induced a p53 mediated apoptosis of lung cancer cells due to a significant reduction in the expression of antioxidant defence proteins (Nrf2 and SOD), Hsp70 (p < 0.02) and Bcl-2 (p < 0.0006), thereby up-regulating reactive oxygen species (ROS) production. This resulted in DNA damage (p < 0.0001), up-regulation of Bax expression and caspase activity and induction of apoptosis in lung cancer cells. The results show the anticancer potential of ECAP on lung cancer. |
| first_indexed | 2024-12-12T03:11:47Z |
| format | Article |
| id | doaj.art-3c9e241ba6864bfe87bce82b20ea2a4a |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T03:11:47Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-3c9e241ba6864bfe87bce82b20ea2a4a2022-12-22T00:40:22ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01107e012987410.1371/journal.pone.0129874Cytotoxic Effect of a Novel Synthesized Carbazole Compound on A549 Lung Cancer Cell Line.Refilwe P MolatlhegiAlisa PhulukdareeKrishnan AnandRobert M GenganCharlette TilokeAnil A ChuturgoonIncreased death rates due to lung cancer have necessitated the search for potential novel anticancer compounds such as carbazole derivatives. Carbazoles are aromatic heterocyclic compounds with anticancer, antibacterial and anti-inflammatory activity. The study investigated the ability of the novel carbazole compound (Z)-4-[9-ethyl-9aH-carbazol-3-yl) amino] pent-3-en-2-one (ECAP) to induce cytotoxicity of lung cancer cells and its mechanism of action. ECAP was synthesized as a yellow powder with melting point of 240-247 °C. The 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), lipid peroxidation and comet assays were used to assess the cytotoxic effect of the compound on A549 lung cancer cells. Protein expression was determined using western blots, apoptosis was measured by luminometry (caspase-3/7, -8 and -9) assay and flow cytometry was used to measure phosphatidylserine (PS) externalisation. ECAP induced a p53 mediated apoptosis of lung cancer cells due to a significant reduction in the expression of antioxidant defence proteins (Nrf2 and SOD), Hsp70 (p < 0.02) and Bcl-2 (p < 0.0006), thereby up-regulating reactive oxygen species (ROS) production. This resulted in DNA damage (p < 0.0001), up-regulation of Bax expression and caspase activity and induction of apoptosis in lung cancer cells. The results show the anticancer potential of ECAP on lung cancer.http://europepmc.org/articles/PMC4489925?pdf=render |
| spellingShingle | Refilwe P Molatlhegi Alisa Phulukdaree Krishnan Anand Robert M Gengan Charlette Tiloke Anil A Chuturgoon Cytotoxic Effect of a Novel Synthesized Carbazole Compound on A549 Lung Cancer Cell Line. PLoS ONE |
| title | Cytotoxic Effect of a Novel Synthesized Carbazole Compound on A549 Lung Cancer Cell Line. |
| title_full | Cytotoxic Effect of a Novel Synthesized Carbazole Compound on A549 Lung Cancer Cell Line. |
| title_fullStr | Cytotoxic Effect of a Novel Synthesized Carbazole Compound on A549 Lung Cancer Cell Line. |
| title_full_unstemmed | Cytotoxic Effect of a Novel Synthesized Carbazole Compound on A549 Lung Cancer Cell Line. |
| title_short | Cytotoxic Effect of a Novel Synthesized Carbazole Compound on A549 Lung Cancer Cell Line. |
| title_sort | cytotoxic effect of a novel synthesized carbazole compound on a549 lung cancer cell line |
| url | http://europepmc.org/articles/PMC4489925?pdf=render |
| work_keys_str_mv | AT refilwepmolatlhegi cytotoxiceffectofanovelsynthesizedcarbazolecompoundona549lungcancercellline AT alisaphulukdaree cytotoxiceffectofanovelsynthesizedcarbazolecompoundona549lungcancercellline AT krishnananand cytotoxiceffectofanovelsynthesizedcarbazolecompoundona549lungcancercellline AT robertmgengan cytotoxiceffectofanovelsynthesizedcarbazolecompoundona549lungcancercellline AT charlettetiloke cytotoxiceffectofanovelsynthesizedcarbazolecompoundona549lungcancercellline AT anilachuturgoon cytotoxiceffectofanovelsynthesizedcarbazolecompoundona549lungcancercellline |